Success rates of treatment for smoking cessation have generally not improved substantially over the past decade. Currently, there is much interest in devising nicotine replacement strategies which provide smokers relief from tobacco withdrawal and thus improve cessation. Despite widespread use of nicotine polacrilex (gum), long-term abstinence rates are still well below 50%. Other new methods are being developed (e.g. transdermal nicotine patch), but it is not yet clear whether they will be better than gum. Thus, additional means of nicotine replacement may be necessary to enhance smoking cessation. The present small grant application is designed to obtain information on the possible utility of a measured-dose nasal spray nicotine delivery procedure, which was developed in our lab as a tool for basic research, in enhancing smoking cessation. This application involves the development of a new treatment technique and represents a new research direction for us, both priority categories for small grants. Three studies using male and female volunteer smokers are planned. Study I involve presenting 0, 7.5, 15, and 30 ug/kg nicotine intermittently to smokers ad then observing amount of cigarette smoking to determine the dose-response effect of nicotine replacement via this method on suppression of ad lib smoking. Study II will determine whether nicotine spray is self-administered to a substantial degree by smokers desiring to quit, and whether intake of the spray relieves tobacco withdrawal. In addition, this study will compare plasma nicotine concentrations, withdrawal relief, and other subjective effects of nicotine spray vs. tobacco smoking to determine the completeness of the nicotine replacement and its effects in comparison to smoking. Finally, Study III will employ this nasal spray procedure to provide nicotine vs. placebo in conjunction with behavioral treatment for smoking cessation to determine the short-term acceptability of nicotine replacement with this method in aiding abstinence. Study III is not designed t be a formal assessment of clinical outcome, given the extensive effort and expense required for such as study, but rather will provide an indication as to whether such a clinical trial is warranted and practical. The knowledge gained from these studies should provide a clear indication as to whether this nasal spray nicotine procedure shows promise as a clinical aid to smoking cessation. If it does show promise (i.e. suppresses smoking in the lab, is self-administered, relieves withdrawal, and provides no practical or safety concerns), we would then propose a larger, more comprehensive evaluation of its clinical utility, including a longer-term clinical trial of cessation.